title: CJY, an isoflavone, interacts with ATPase of P-glycoprotein in the rat brain microvessel endothelial cells (RBMECs).
abstract: Our previous study reported CJY, an isoflavone, can reverse P-glycoprotein (P-gp) efflux activity in rat brain microvessel endothelial cells (RBMECs). In the present report, by assessment of ATPase activity of RBMECs, we gained further insight into the nature of the CJY interactions with P-gp. The results revealed that the basal P-gp ATPase activity was increased by CJY. Kinetic studies on ATPase activity showed the effects of Tetrandrine (Tet) on CJY-stimulated, CsA on CJY-stimulated, and CsA on Tet-stimulated P-gp ATPase activity were all non-competitive inhibition, indicating that these substrates can simultaneously but independently bind to diverse sites on P-gp. Furthermore, the combined effects of CJY with Tet, and CJY with CsA were also evaluated isobolographically. The results showed synergistic interactions in both combinations, implying that combined treatment of CJY with other modulators may exert synergistic interactions for the drug's penetration into the brain and the treatment of neurological disorders.
authors.forename: Ming-Shan
authors.initials: MS
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Cen
authors.forename: Ling
authors.initials: L
authors.lastname: He
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Bian-Sheng
authors.initials: BS
authors.lastname: Ji
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D044182:Benzylisoquinolines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002460:Cell Line; D004357:Drug Synergism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D007700:Kinetics; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D044182:Benzylisoquinolines; D007529:Isoflavones; C009438:tetrandrine; D000251:Adenosine Triphosphatases
keywords: Brain microvessel endothelial cells; CJY,; P-glycoprotein,; P-gp ATPase,